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The cascade of inflammation and cell death that occurs immediately following stroke drives vascular and functional loss that does not fully recover over time, and no Food and Drug Administration (FDA)\u2010approved therapies exist that stimulate regeneration post\u2010stroke. A hyaluronic acid (HA)\u2010based hydrogel was previously developed that delivered heparin nanoparticles alone, to reduce glial reactivity, and heparin nanoparticles with vascular endothelial growth factor (VEGF) bound to their surface, to promote angiogenesis. However, the inclusion of the naked heparin nanoparticles warranted concern over the development of bleeding complications. Here, it is explored how microporous annealed particle (MAP) scaffolds functionalized with VEGF coated heparin nanoparticles can both reduce glial reactivity and promote angiogenesis \u2013 without the inclusion of free heparin nanoparticles. It is showed that the updated design successfully promotes de novo tissue formation, including the development of mature vessels and neurite sprouting, and leads to functional improvement in a photothrombotic stroke model. In addition, increased astrocyte infiltration is found into the infarct site correlated with mature vessel formation. This work demonstrates how the biomaterial design can enhance endogenous regeneration post\u2010stroke while eliminating the need for excess heparin.<\/jats:p>","DOI":"10.1002\/adfm.202500696","type":"journal-article","created":{"date-parts":[[2025,3,20]],"date-time":"2025-03-20T05:51:32Z","timestamp":1742449892000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Delivery of Angiogenic Therapy from Flowable Hyaluronic Acid Porous Scaffolds Results in Functional Improvement without Anti\u2010Inflammatory Agents"],"prefix":"10.1002","volume":"35","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0790-8447","authenticated-orcid":false,"given":"Kevin","family":"Erning","sequence":"first","affiliation":[{"name":"Department of Biomedical Engineering Duke University  Durham NC 27708\u20100281 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1389-1327","authenticated-orcid":false,"given":"Katrina L.","family":"Wilson","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering Duke University  Durham NC 27708\u20100281 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6085-5145","authenticated-orcid":false,"given":"Cara S.","family":"Smith","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering Duke University  Durham NC 27708\u20100281 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-2066-9078","authenticated-orcid":false,"given":"Long","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering Duke University  Durham NC 27708\u20100281 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-2811-0535","authenticated-orcid":false,"given":"Neica I.","family":"Joseph","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering Duke University  Durham NC 27708\u20100281 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-6236-7003","authenticated-orcid":false,"given":"Rachel","family":"Irengo","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering Duke University  Durham NC 27708\u20100281 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-2437-3972","authenticated-orcid":false,"given":"Lauren Y.","family":"Cao","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering Duke University  Durham NC 27708\u20100281 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohanapriya","family":"Cumaran","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering Duke University  Durham NC 27708\u20100281 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-2830-3950","authenticated-orcid":false,"given":"Yi","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering Duke University  Durham NC 27708\u20100281 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-1702-3714","authenticated-orcid":false,"given":"Sihan","family":"Lyu","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering Duke University  Durham NC 27708\u20100281 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-0503-7136","authenticated-orcid":false,"given":"Lindsay","family":"Riley","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering Duke University  Durham NC 27708\u20100281 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9381-4630","authenticated-orcid":false,"given":"Timothy W.","family":"Dunn","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering Duke University  Durham NC 27708\u20100281 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1169-9203","authenticated-orcid":false,"given":"S. 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